Elena Huerga

Autonomous University of Barcelona, Cerdanyola del Vallès, Catalonia, Spain

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Publications (13)87.85 Total impact

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    ABSTRACT: Background: A pseudoatrophy effect has been held responsible for the lack of net impact of natalizumab on brain volume outcomes in 2-year trials, but no data are available beyond 24 months. Objective: We aimed to investigate brain volume dynamics in natalizumab-treated patients in up to 3 years after therapy initiation with clinical correlations. Methods: Patients on natalizumab for at least 3 years were clinically assessed 3-monthly. Magnetic resonance imaging scans were performed at baseline and yearly. Brain volume changes were obtained with SIENA. Multivariate models were used to investigate the association between baseline inflammation and changes in brain volume and disability. Results: Sixty-two patients with multiple sclerosis were analysed. Mean age and disease duration were 34.7 (SD: 8.3) and 10.4 (SD: 6.6) years. Presence of gadolinium enhancement at baseline was not associated with Expanded Disability Status Scale changes (p=0.468), but was associated with larger brain volume decreases (p=0.005) in the first (p=0.024) and second year (p=0.019) but not in the third year (p=0.863). Brain volume changes at 12 and 36 months were marginally associated with disability status at month 12 (p=0.094) and 36 (p=0.084), respectively. Conclusions: Baseline inflammation affects brain volume measures up to 24 months after natalizumab initiation. A marginal association of brain volume changes with disability is present.
    No preview · Article · Nov 2014 · Multiple Sclerosis

  • No preview · Conference Paper · May 2014
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    ABSTRACT: Non-enhancing black holes (neBHs) are more common in multiple sclerosis (MS) patients with longer disease durations and progressive disease subtypes. Our aim was to analyse the added value of neBHs in patients with clinically isolated syndromes (CISs) for predicting conversion to clinically definite MS (CDMS). Patients were classified based on the presence or absence of neBHs and on the number of Barkhof-Tintoré (B-T) criteria fulfilled. Dissemination in space (DIS) was defined as the presence of at least three of the four B-T criteria. Dissemination in time (DIT)1 was defined by simultaneous presence of enhancing and non-enhancing lesions. DIT2 was defined by simultaneous presence of neBHs and T2 lesions not apparent on T1-weighted images. Focal T2-hyperintense brain lesions were identified in 87.7% of the 520 CIS patients, and 41.4% of them presented at least one neBH. Patients meeting DIS, DIT1, and DIT2 had a significantly higher rate of conversion to CDMS. After adjusting for DIS, only patients who fulfilled DIT1 preserved a significant increase in CDMS conversion. Non-enhancing black holes in CIS patients are associated with a higher risk of conversion to CDMS. However, the predictive value of this finding is lost when added to the DIS criteria.
    No preview · Article · Feb 2014 · Multiple Sclerosis
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    ABSTRACT: BACKGROUND: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. OBJECTIVES: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. METHODS: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. RESULTS: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (- 0.65% versus + 0.059%; p < 0.001). PBVC decreases below - 0.817% independently predicted shorter times to a second attack. CONCLUSIONS: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.
    No preview · Article · May 2013 · Multiple Sclerosis
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    ABSTRACT: DTI has shown increased MD of water molecules in the brain of patients with cirrhosis, consistent with low-grade edema. This study further characterizes this edema by using biexponential analysis of DTI data, a technique that may differentiate cytotoxic and vasogenic edema. A total of 41 patients with cirrhosis awaiting liver transplantation and 16 healthy controls were studied by DTI by using a single-shot echo-planar technique with 11 b-values (range, 0-7500 s/mm(2)) and 6 noncollinear directions. Measurements were fitted to biexponential function to determine MD and FA for the fast and slow diffusion components. Regions of interest were selected in the parietal white matter and corticospinal tract. The assessment was repeated 1 year after liver transplantation in 24 of these patients. In parietal white matter, patients with cirrhosis showed an increase in fast MD and a decrease in fast FA that normalized after liver transplantation. In the corticospinal tract, there was an increase in fast and slow MD that normalized after transplantation, and a decrease in FA that persisted posttransplantation. There was no association of DTI parameters with minimal HE (n =12). Biexponential analysis of DTI supports the presence of edema in the brain of patients with cirrhosis that reverts after transplantation. In parietal white matter, the increase in brain water was mainly located in the interstitial compartment, while the corticospinal tract showed a mixed pattern (intra- and extracellular). In addition, the findings on posttransplantation were consistent with microstructural damage along the corticospinal tract.
    Full-text · Article · Jun 2011 · American Journal of Neuroradiology
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    ABSTRACT: To analyse the safety and effectiveness of natalizumab in the treatment of multiple sclerosis in a real clinical practice setting and according to the approved indications. All patients with multiple sclerosis treated with natalizumab in our centre were evaluated. The clinical and radiological disease activity during the first year of treatment was analyzed in patients who received at least 12 doses of the drug. The data regarding moderate and severe adverse events in the entire study sample was also evaluated. A total of 112 patients were included in the study, of which 110 had been previously treated with other drugs and 76 had received at least 12 doses of natalizumab. In this group, the annualized relapse rate was reduced by 89% compared to the preceding year and 80% of patients were free from relapses after one year of treatment. Nine percent of patients exhibited 3-month confirmed disability progression. At month 12, the mean number of gadolinium-enhancing lesions on brain MRI was decreased by 99% compared to the pre-treatment MRI. During the first year of treatment, 76% of patients remained free from clinical activity and 33% remained free from both clinical and radiological disease activity. Twenty-nine percent of patients had at least one moderate or severe adverse event, which led to treatment discontinuation in 6%. Four percent of patients experienced immediate hypersensitivity reactions. This study suggests that natalizumab is effective in reducing disease activity in patients with relapsing multiple sclerosis and inadequate response to other therapies, with a favorable risk-benefit ratio.
    No preview · Article · Mar 2011 · Revista de neurologia
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    ABSTRACT: Different double inversion recovery (DIR) sequences are currently used in multiple sclerosis (MS) research centers to visualize cortical lesions, making it difficult to compare published data. This study aimed to formulate consensus recommendations for scoring cortical lesions in patients with MS, using DIR images acquired in 6 European centers according to local protocols. Consensus recommendations were formulated and tested in a multinational meeting. Cortical lesions were defined as focal abnormalities on DIR, hyperintense compared to adjacent normal-appearing gray matter, and were not scored unless ≥ 3 pixels in size, based on at least 1.0 mm(2) in-plane resolution. Besides these 2 obligatory criteria, additional, supportive recommendations concerned a priori artifact definition on DIR, use of additional MRI contrasts to verify suspected lesions, and a constant level of displayed image contrast. Robustness of the recommendations was tested in a small dataset of available, heterogeneous DIR images, provided by the different participating centers. An overall moderate agreement was reached when using the proposed recommendations: more than half of the readers agreed on slightly more than half (54%) of the cortical lesions scored, whereas complete agreement was reached in 19.4% of the lesions (usually larger, mixed white matter/gray matter lesions). Although not designed as a formal interobserver study, the current study suggests that comparing available literature data on cortical lesions may be problematic, and increased consistency in acquisition protocols may improve scoring agreement. Sensitivity and specificity of the proposed recommendations should now be studied in a more formal, prospective, multicenter setting using similar DIR protocols.
    No preview · Article · Feb 2011 · Neurology
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    ABSTRACT: Number of baseline lesions has been shown to predict future attacks and disability in clinically isolated syndromes (CIS). To investigate the role of baseline infratentorial lesions in long-term prognosis. Subjects were included in a prospective cohort of patients with CIS. Patients underwent brain MRI within 3 months after CIS onset. Number and location of lesions at baseline were prospectively studied. Retrospective scan analysis was conducted to specifically look at number and location of infratentorial lesions. We analyzed the time to a second attack and to reach EDSS 3.0. We included 246 patients with CIS followed for a median of 7.7 years. Patients with infratentorial lesions had both a higher risk of conversion (71.4% vs 29.6%; hazard ratio [HR] 3.3; 95% confidence interval [CI] 2.2-4.8; p < 0.001) and of developing disability (32.5% vs 12.4%; HR 2.4; 95% CI 1.3-4.3; p = 0.003). Presence of at least one cerebellar lesion was associated with an increased risk of conversion (HR 2.4; 95% CI 1.3-4.5; p = 0.007). Presence of at least one brainstem lesion increased both the risk of conversion (HR 2.9; 95% CI 1.7-5.0; p < 0.001) and disability (HR 2.5; 95% CI 1.1-5.4; p = 0.026). Broken down into number of lesions, the presence of infratentorial lesions increased both the risk of conversion (83% vs 61%) (HR 22.3; 95% CI 9.7-51.1; p < 0.001) and of reaching EDSS 3.0 (40% vs 19%) (HR 3.2; 95% CI 1.3-7.4; p = 0.008) only in patients with 9 or more lesions. Presence of infratentorial lesions increases the risk for disability. Brainstem rather than cerebellar lesions may be responsible for poor prognosis.
    No preview · Article · Nov 2010 · Neurology
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    ABSTRACT: A prolonged survival in liver transplant recipients due to a better management exposes them to multiple factors that can impair neurologic function in the long term. Twenty-two patients were studied by brain magnetic resonance and completed a neuropsychologic assessment shortly before liver transplant, 6 to 12 months after (short term), and 6 to 9 years (long term) after liver transplant. Thirteen healthy controls matched by age were studied in parallel. An enlargement in the ventricular size (an indirect measure of brain volume) was observed in the short term (+8%) and in the long term after liver transplant (+22%); the size of ventricles was larger than in healthy controls. In addition, a progression in the volume of focal T2 white matter lesions (an index of small vessel cerebrovascular disease) was detected in the long term (+49%) and was related to vascular risk factors in those with larger increases (>12.5% per year). Neuropsychologic function showed a significant improvement after liver transplant and remained stable in the long term, except for memory loss in those patients with larger increases in white matter lesions. Improvement in neuropsychologic function after successful liver transplant can be demonstrated up to 9 years. However, these patients experience a progressive accumulation of focal T2 brain lesions and show a smaller brain volume than controls, which can be related to their previous cirrhosis. A good management to minimize brain injury before transplantation and an accurate treatment of vascular risk factors may be important to prevent consequences on cognitive function.
    Full-text · Article · Mar 2010 · Transplantation
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    ABSTRACT: A diagnosis of multiple sclerosis in patients who present for the first time with a clinically isolated syndrome (CIS) can be established with brain magnetic resonance imaging (MRI) if the MRI demonstrates demyelinating lesions with dissemination in space (DIS) and dissemination in time (DIT). To investigate the diagnostic performance of a single MRI study obtained within the first 3 months after symptom onset in a cohort of patients with a CIS suggestive of multiple sclerosis at presentation. Multicenter inception cohort with a follow-up of at least 24 months. Referral hospitals. Patients Patients with CIS onset between April 1, 1995, and September 30, 2004, who fulfilled the following criteria were included: (1) age of 14 to 50 years and (2) clinical follow-up for at least 24 months after CIS onset or until development of clinically definite multiple sclerosis (CDMS), if this occurred within 2 years. Main Outcome Measure All patients underwent 2 comparable brain MRI examinations, the first within 3 months (early) and the second between 3 and 12 months (delayed) after CIS onset. We defined DIS using several existing MRI criteria, and DIT was inferred when there were simultaneous gadolinium-enhancing and nonenhancing lesions on a single MRI. Two hundred fifty patients were included in the study. The comparison of the diagnostic performance of various MRI criteria for identifying early converters to CDMS showed similar sensitivity and specificity between early and delayed MRIs. In addition, the use of less stringent criteria for DIS yielded better sensitivity and similar specificity, particularly when assessed in the first weeks after CIS onset. A single brain MRI study that demonstrates DIS and shows both gadolinium-enhancing and nonenhancing lesions that suggest DIT is highly specific for predicting the early development of CDMS, even when the MRI is performed within the first 3 months after the onset of a CIS.
    Full-text · Article · Jun 2009 · Archives of neurology
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    ABSTRACT: Our objective in this study is to evaluate whether brain magnetic resonance imaging (MRI) performed at interferon-beta (IFN-beta) onset and after 12 months allow us to identify relapsing-remitting multiple sclerosis (RRMS) patients with a disability increase in the first 2 years of therapy. This is a prospective and longitudinal study of patients with RRMS treated with IFN-beta. All patients included underwent brain MRI before the onset of therapy with IFN-beta and 12 months after. MRI measures (T2, unenhanced T1-weighted and gadolinium-enhancing T1-weighted brain lesion load, brain parenchymal fraction) were undertaken at baseline and after 12 months. The number of active lesions (new or enlarging T2 plus gadolinium-enhancing brain lesions) was also assessed on the 12 months MRI scan. Expanded Disability Status Scale (EDSS) was scored every 3 months. We defined an increase in disability as an increase of at least 1 EDSS point confirmed and sustained during the first 2 years of therapy with IFN-beta. Regression analysis was performed in order to identify MRI variables of response. We included 152 patients who were followed-up for at least 2 years. After 2 years of therapy, 24 patients (16%) had an increase in disability. The logistic regression model showed that active lesions in the scan performed at 12 months were the most important factor related with the increase of disability after 2 years of therapy (odds ratio 8.3, 95% confidence interval 3.1-21.9; p < 0.0001). In RRMS patients treated with IFN-beta the MRI changes occurring during the first year may have a prognostic value for identifying patients with a confirmed increase of disability after 2 years of therapy.
    No preview · Article · May 2008 · Multiple Sclerosis
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    ABSTRACT: Focal T2-weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small-vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2-weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm(3) to 0.671 cm(3), P = 0.001). This decrease correlated with an improvement in an index of global cognitive function (r = -0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. CONCLUSION: Focal WML probably induced by age-related microvascular injury can decrease their volume with liver transplantation. The associated improvement of cognitive function supports a relationship between brain edema and minimal hepatic encephalopathy.
    Full-text · Article · Nov 2007 · Hepatology
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    ABSTRACT: The 2001 and 2005 McDonald criteria allow MRI evidence for dissemination in space (DIS) and dissemination in time (DIT) to be used to diagnose multiple sclerosis in patients who present with clinically isolated syndromes (CIS). In 2006, new criteria were proposed in which DIS requires at least one T2 lesion in at least two of four locations (juxtacortical, periventricular, infratentorial, and spinal-cord) and DIT requires a new T2 lesion on a follow-up scan. We applied all three criteria in a large cohort of CIS patients to assess their performance by use of conversion to clinically definite multiple sclerosis (CDMS) as the outcome. Patients who had two MRI scans within 12 months of CIS onset were identified in four centres in the Magnims European research network. The specificity and sensitivity of MRI criteria for CDMS after 3 years was assessed in 208 patients. A Cox proportional hazards model was applied in a larger cohort of 282 patients that included all patients irrespective of length of follow-up. The specificity of all criteria for CDMS was high (2001 McDonald, 91%; 2005 McDonald, 88%; new, 87%). Sensitivity of the new (72%) and 2005 McDonald (60%) criteria were higher than the 2001 McDonald criteria (47%). The Cox proportional hazards model showed a higher conversion risk for all three criteria in those with both DIS and DIT than those with either DIS or DIT alone. When all three criteria were included in the model, only the new criteria had an independent significant effect on conversion risk. The new criteria are simpler than the McDonald criteria without compromising specificity and accuracy. The presence of both DIS and DIT from two MRI scans has a higher specificity and risk for CDMS than either DIS or DIT alone.
    No preview · Article · Sep 2007 · The Lancet Neurology

Publication Stats

582 Citations
87.85 Total Impact Points


  • 2009-2014
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
  • 2007-2014
    • University Hospital Vall d'Hebron
      • • Department of Neurology
      • • Department of Radiology
      Barcino, Catalonia, Spain
  • 2011
    • Hospital Valle Del Nalon
      Rianxo, Galicia, Spain